In order to understand the mechanisms of action of narcotic analgesics and antagonists, biochemical changes associated with the cellular adaptation of brain to narcotics must be delineated. Eneregy metabolism in brain is one of the most important aspects of these basic mechanisms, but the chronology of changes in metabolism has yet to be mapped out in laboratory animals given a variety of doses and regimens of representative narcotics and antagonists. Sensitive enzymatic, fluorimetric assays and rapid freezing techniques will be used in mouse and rat brain to study the relationship of changes in specific substrates and enzymes of aerobic and anaerobic metabolism of glucose to the development of antinociception, tolerance, and physical dependence.